Maternal miRNA-146a G/C rs2910164 variation, HIV/AIDS and nitrogen oxide pollution exposure collectively affects foetal growth.

OBJECTIVE:: Nitrogen oxide (NOx) pollution and human immunodeficiency virus (HIV)/AIDS intensify inflammation during pregnancy and linked with adverse birth outcomes (ABOs). MicroRNA (miRNA)-146a plays a crucial role in regulating inflammation in the NF-κB pathway. The G/C rs2910164 dampens miRNA-146a activity and linked with inflammatory diseases. The present study investigated whether HIV/AIDS and NOx exposure throughout pregnancy further intensifies ABO in Black South African women genotyped for the rs2910164. METHODS:: Pregnant women ( n = 300) were subdivided into low, medium and high NOx exposure groups, genotyped for the miRNA-146a G/C rs2910164 using polymerase chain reaction-restriction fragment length polymorphism, and further stratified based on HIV status. RESULTS:: Unstratified data (HIV+ and HIV- mothers combined): Mothers from the high NOx group with the variant C-allele had low blood iron levels ( p = 0.0238), and had babies with reduced birthweights ( p = 0.0283). As NOx increased, the prevalence of preterm birth and low birth weight also increased in mothers with the variant C-allele versus wildtype G-allele. HIV-infected mothers: In all NOx exposure groups, mothers with the variant C-allele had higher systolic blood pressure (low: p = 0.0386, medium: p = 0.0367 and high: p = 0.0109) and had babies with lower Appearance, Pulse, Grimace, Activity and Respiration scores at 1 min (low: p = 0.0190, medium: p = 0.0301 and high: p = 0.0361). CONCLUSION:: Maternal rs2910164 variant C-allele, NOx pollution and HIV/AIDS might collectively play a role in intensifying gestational hypertension and ABO.

IL-17A[G197G]-Association between NOx and gestational age in a South African birth cohort.

Interleukin (IL-)17A, plays a role in pathogenic defence, but is implicated in chronic inflammatory diseases, and has recently been associated with variable pregnancy outcomes. We investigated the role of maternal IL-17-[G197A]-specific effects of third-trimester IL-17 mRNA expression, NOx exposure levels and other variables on gestational age, in the Mother and Child in the Environment (MACE) birth cohort in South Africa. A total of 327 participants were genotyped for IL-17-[G197A] by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to quantitate IL-17-mRNA expression in whole blood. Multivariate linear regression analysis, stratified by IL-17-[G197A] genotype, was used to test for effects of NOx , IL17A/GAPDH, haemoglobin, body mass index, HIV-1 positivity, maternal education and income level on gestational age. Lower expression was associated with the IL-17-GG versus GA in the cohort and HIV-1-negative group (p = .0007, p = .0058), while no difference was observed in the HIV-1 positives. Elevated IL-17A expression was observed in the high NOx exposure groups, within IL-17[G197G] (p = .0004). IL-17[G197G] was associated with PTB (p < .0001), and the PTB group had lower IL-17A expression compared to the full-term group (p = .0002). IL-17 expression was associated with an increase in gestational age (p = .038), and NOx was associated with a decrease in gestational age in the IL-17[G197G] model (p = .046).

IL-1ß haplotype influences the effect of NOx exposure on gestational age in the South African MACE birth cohort.

OBJECTIVE: Cytokines, molecules within the immune system that affect either a pro- or anti-inflammatory response, have previously been shown to influence birth outcomes. The maternal cytokine gene-environment interactions are thought to alter their expression, potentially influencing susceptibility to adverse birth outcomes. The aim of this study was to determine the association between the maternal interleukin-1ß (IL-1ß) haplotype and expression variation with oxides of nitrogen (NOx) levels, and thereafter investigate the IL-1ß haplotype-specific effects of NOx exposure levels, IL-1ß mRNA expression and other variables on gestational age. MATERIAL AND METHODS: Using the prospective Mother and Child in the Environment (MACE) birth cohort in Durban, South Africa, 335 participants were genotyped for the IL-1ß haplotype. Previous studies showed that three single nucleotide polymorphisms (SNPs), IL-1ß-1464G/C, -511C/T and -31C/T, constitute the IL-1ß functional haplotype. These SNPs were genotyped using a restriction fragment length polymorphism assay, while IL-1ß mRNA expression was measured using a quantitative real-time polymerase chain reaction assay. Individual estimates of NOx exposure were obtained by land use regression modelling. A multivariate linear regression analysis was employed to test for significant effects on gestational age. RESULTS: IL-1ß mRNA expression was found to possess a haplotype-dependent effect ( p = 0.0001) and its expression levels positively correlated with NOx levels ( r = 0.34; p = 0.006). In the high haplotype model, a unit increase in NOx exposure level was associated with a decrease in gestational age by 1 week ( p = 0.02). Furthermore, gestational age decreased by 0.9 weeks for every unit increase of IL-1ß mRNA expression level ( p = 0.025). HIV-1 positivity was associated with a 0.2-week decrease in gestational age ( p = 0.035) in the intermediate haplotype model and a 0.4-week decrease in the high haplotype model ( p = 0.044). CONCLUSION: These data have implications for better understanding the effect of prenatal NOx exposure on gestational age and demonstrate the role of the IL-1ß haplotype in modulating the effects of NOx exposure.

Petrol exposure and DNA integrity of peripheral lymphocytes.

PURPOSE: To determine the effect of petrol exposure on DNA integrity in peripheral blood lymphocytes among petrol attendants and a non-exposed comparison population. METHODS: This cross-sectional study included 101 fuel station employees and 50 office-based non-exposed workers in Durban, South Africa. Participants were interviewed using a validated questionnaire. Genomic DNA was extracted from peripheral lymphocytes for the benzo(a)pyrene diol epoxide (BPDE)-DNA adduct assay (ELISA), and DNA damage was determined using the comet assay and reported as percentage tail DNA. RESULTS: The exposed (n = 101) and non-exposed participants (n = 50) varied with regard to age, housing, smoking, and proximity to industry and petrol stations. Among the exposed, the mean duration of employment in the fuel industry was 5.8 years (SD = 4.6), and among those pumping fuel (n = 75), the mean metric tons of petrol pumped in the past 12 months per worker was 199.2 (SD = 88.9). The mean percentage tail DNA varied significantly between exposed and non-exposed groups: 23.8 % (SD = 13.3) and 8.1 % (SD = 1.8) (p < 0.01), respectively. A significant difference existed between the groups for BPDE-DNA adducts: 30.0 ng/ml (SD = 12.7) and 18.1 ng/ml (SD = 18.2) (p < 0.0001), respectively. Regression models, adjusting for cigarette smoking, age, and sex, showed a 16.5 greater percentage tail DNA among the exposed compared to non-exposed (95 % CI 11.8-21.1 %), while the exposed group had a 12.9 ng/ml greater increase in BPDE-DNA adducts has compared to the unexposed (95 % CI 7.2-18.7 ng/ml). Cigarette smoking resulted in almost a 3.5 % increase in percentage tail DNA. CONCLUSION: Our study adds to the literature that long-term, low-dose exposure to vehicular fuels is likely to result in altered DNA integrity and genotoxicity among petrol attendants. These results strengthen the case that these workers must be afforded appropriate protection to prevent serious adverse outcomes.